Comprehensive Analysis of Immune-Related Prognosis of TK1 in Hepatocellular Carcinoma.
Increased expression of TK1 is associated with the progression of a variety of tumors. However, the relationship of TK1 expression with immune cell infiltration and its prognostic value in hepatocellular carcinoma (HCC) are still unknown. In this study the TCGA database was used to evaluate TK1 expression and its impact on survival in patients with HCC. Compared with normal tissue, TK1 in the liver tissue of patients with HCC was significantly up-regulated at both the mRNA and protein levels. Furthermore, TK1 expression was significantly related to pathological stage, tumor stage and lymph node metastasis, with high TK1 expression being an unfavorable prognostic factor for HCC. TK1 expression was also significantly associated with the infiltration of B cells, T cells, and dendritic cells in HCC. Single-cell sequencing analysis revealed that TK1 was associated with relatively large changes in T cells, especially gamma-delta T cells. A prognostic risk score based on TK1-related immune genes (CD40LG and TNFRSF4) was established using COX regression analysis. By integrating the immune-related risk score model with clinical features, a nomogram was constructed to predict the survival rate of HCC patients (1 year, 3-year and 5-year AUC of 0.782, 0.783 and 0.771, respectively). Knockdown of the target gene for TK1 was found to have significant anti-apoptosis and pro-proliferation effects on HepG2 cells. The level of TK1 in the serum and liver tissue of patients with HCC was significantly increased relative to healthy controls. These findings highlight the role of TK1 in the tumor immune response of HCC patients and in the proliferation and apoptosis of HepG2 cells. TK1 could therefore be a potential immunotherapy target for HCC patients, while the two immune genes related to TK1 (CD40LG And TNFRSF4) may be promising prognostic biomarkers in HCC.


Validation of spontaneous abortion diagnoses in the Danish National Registry of Patients.
The purpose of this study is to validate the diagnosis of spontaneous abortion (SA) recorded in the Danish National Registry of Patients (DNRP). We randomly selected patients registered in the DNRP with a diagnosis of SA between 1980 and 2008 from hospitals in the county of North Jutland and searched for their discharge records in hospital files. We estimated positive predictive value (PPV) of the DNRP diagnosis and stratified the analysis by period (1980-1994 versus 1995-2008), hospital type (regional versus local), and International Classification of Diseases revisions (ICD-8 versus ICD-10). We could identify hospital files of 117/174 (67%) sampled registration records. Of those, the diagnosis was confirmed in 114 patients, yielding a PPV of 97.4% (95% confidence interval = 92.7%-99.5%). The PPV did not markedly vary by period, hospital type, or ICD revision. Among the three patients with available data who did not fulfill the criteria for SA, one had an induced abortion and two had threatened abortion but did not miscarry. Registration of SA in the DNRP accurately reflects the diagnoses recorded in medical charts. The DNRP is a suitable source of data on SAs for epidemiologic research.


Molecular pathways used by platelets to initiate and accelerate atherogenesis.
The response to injury model in the development of atherosclerosis is broadly accepted by the scientific audience. Platelets are generally not believed to be involved in the initiation of atherosclerosis. New data imply, however, that the response to injury model is too simple for a complete understanding of the inflammatory disease atherosclerosis. The involvement of platelets in the initiation of atherosclerotic lesion formation is critical in directing the atherosclerotic process into regeneration or ongoing vascular injury. Platelets internalize oxidized phospholipids and promote foam cell formation. Platelets also recruit circulating blood cells including progenitor cells to the vessel, that are able to differentiate into foam cells or endothelial cells depending on conditions. Platelets express various scavenger receptors that are able to regulate LDL-uptake. LDL-laden platelets are internalized by adherent progenitor cells that in turn differentiate into macrophages and foam cells. An expanding body of evidence continues to build on the role of platelets as initial actors in the development of atherosclerotic lesions. Platelets bind to leukocytes, endothelial cells, and circulating progenitor cells and initiate monocyte transformation into macrophages. Therefore platelets regulate the initiation, development and total extent of atherosclerotic lesions.


Risk of pneumonia among patients with chronic kidney disease in outpatient and inpatient settings: a nationwide population-based study.
Patients with chronic kidney disease (CKD) are more at risk for pneumonia than the general population. Patients with pneumonia are usually treated as outpatients. However, previous studies were conducted on the basis of inpatient pneumonia. This method may underestimate the risk of pneumonia in patients with CKD. Therefore, we investigated the risk of pneumonia among CKD patients in both outpatient and inpatient settings. A total of 15,562 patients with CKD and 62,109 individuals without CKD (matched for age and gender) were taken as subjects in the Longitudinal Health Insurance Database of Taiwan National Insurance from 1996 to 2010. The incidence density rates of inpatient and outpatient pneumonia were calculated. The risk factors associated with pneumonia were analyzed using Cox proportional hazard models with adjustments for confounders. The incidence density rate of pneumonia was 65.6 per 1000 person-years in patients with CKD and 28.4 per 1000 person-years in individuals without CKD. The incidence density rate of inpatient pneumonia was 43.3 per 1000 person-years in patients with CKD and 16.6 per 1000 person-years in individuals without CKD. CKD was associated with increased risk of pneumonia (adjusted hazard ratio [aHR], 1.97; 95% confidence interval [CI], 1.89-2.05; P < 0.001), outpatient pneumonia (aHR, 1.40; 95% CI, 1.31-1.49), and inpatient pneumonia (aHR, 2.17; 95% CI, 2.07-2.29, P < 0.001). Patients' comorbidities, including diabetes, cardiovascular disease (CVD), asthma, and chronic obstructive pulmonary disease (COPD), were independently associated with increased risk of pneumonia.CKD is associated with the increased risk of both outpatient and inpatient pneumonia. This association is independent of comorbid diabetes, CVD, asthma, and COPD.


[Cardiomyoplasty--a surgical method of treatment in heart failure].
Until recently heart transplantation has been the only method of surgical treatment of severe myocardial heart failure. In the recent years operations of cardiomyoplasty have been performed more and more often for treatment of patients with this disease. The article presents the literature and personal data on the operation technique, indications and contraindications for it. First clinical results of the operative interventions fulfilled since 1994 are discussed.


Production of soluble truncated spike protein of porcine epidemic diarrhea virus from inclusion bodies of Escherichia coli through refolding.
The emergence of highly pathogenic variant porcine epidemic diarrhea virus (PEDV) strains, from 2013 to 2014, in North American and Asian countries have greatly threatened global swine industry. Therefore, development of effective vaccines against PEDV variant strains is urgently needed. Recently, it has been reported that the N-terminal domain (NTD) of S1 domain of PEDV spike protein is responsible for binding to the 5-N-acetylneuraminic acid (Neu5Ac), a possible sugar co-receptor. Therefore, the NTD of S1 domain could be an attractive target for the development of subunit vaccines. In this study, the NTD spanning amino acid residues 25-229 (S25-229) of S1 domain of PEDV variant strain was expressed in Escherichia coli BL21 (DE3) in the form of inclusion bodies (IBs). S25-229 IBs were solubilized in 20 mM sodium acetate (pH 4.5) buffer containing 8 M urea and 1 mM dithiothreitol with 95% yield. Solubilized S25-229 IBs were refolded by 10-fold flash dilution and purified by one-step cation exchange chromatography with >95% purity and 20% yield. The CD spectrum of S25-229 showed the characteristic pattern of alpha helical structure. In an indirect ELISA, purified S25-229 showed strong reactivity with mouse anti-PEDV sera. In addition, immunization of mice with 20 μg of purified S25-229 elicited highly potent serum IgG titers. Finally, mouse antisera against S25-229 showed immune reactivity with native PEDV S protein in an immunofluorescence assay. These results suggest that purified S25-229 may have potential to be used as a subunit vaccine against PEDV variant strains.


Numerical study on a micro prism and micro lenses with metal-dielectric multilayered structures.
A micro optical prism and micro lenses with metal-and-dielectric multilayered subwavelength structure (MDMS) are discussed. The MDMS prism has a highly dispersive optical property. Light waves do not spread out in the small prism because of the restriction of propagation direction of light. Optical properties of a curved MDMS prism were investigated by theoretical analysis and numerical simulations. The curved MDMS prism with a structure period of 0.4 microm and an apex angle of 90 degrees had angular dispersion of 0.11 degrees /nm for light of 1.5 microm wavelength. A convexo-plane MDMS lens and a gradient-index MDMS lens were also investigated, and the optical behavior for the curved prism with the convexo-plane lens was demonstrated by a numerical simulation.


Homozygosity for a gross partial gene deletion of the C-terminal end of ATP7B in a Wilson patient with hepatic and no neurological manifestations.
We identified a partial gene deletion of ATP7B in a patient with Wilson disease with hepatic onset. The deletion covered exon 20 including major parts of the flanking introns. The breakpoints were identified and the size of the deletion determined to be 2144 bp. The deletion is predicted to lead to a mutated protein product containing 45 aberrant amino acids after transmembrane domain 7, and lacking the transmembrane domain 8 as well as the entire C-terminal cytoplasmic tail. This is the first time a partial gene deletion has been demonstrated in ATP7B. The patient presented at age 10 with hepatic manifestations, including severe jaundice, hepato-splenomegaly, ascites, and spider naevi. The liver biopsy showed fibrosis and early signs of cirrhosis. There was a Kayser-Fleischer ring but no neurological manifestations. All symptoms disappeared with penicillamine therapy. This suggests that the C-terminal cytoplasmatic tail of ATP7B, is not essential for its neurological function. Large deletions in ATP7B may be an overlooked cause of Wilson disease. Patients that are homozygotes for deletions may be valuable for the understanding of the function of various regions of the ATP7B protein.


Are reports of randomized controlled trials improving over time? A systematic review of 284 articles published in high-impact general and specialized medical journals.
Inadequate reporting undermines findings of randomized controlled trials (RCTs). This study assessed and compared articles published in high-impact general medical and specialized journals. Reports of RCTs published in high-impact general and specialized medical journals were identified through a search of MEDLINE from January to March of 1995, 2000, 2005, and 2010. Articles that provided original data on adult patients diagnosed with chronic conditions were included in the study. Data on trial characteristics, reporting of allocation concealment, quality score, and the presence of a trial flow diagram were extracted independently by two reviewers, and discrepancies were resolved by consensus or independent adjudication. Descriptive statistics were used for quantitative variables. Comparisons between general medical and specialized journals, and trends over time were performed using Chi-square tests. Reports of 284 trials were analyzed. There was a significantly higher proportion of RCTs published with adequate reporting of allocation concealment (p = 0.003), presentation of a trial flow diagram (p<0.0001) and high quality scores (p = 0.038) over time. Trials published in general medical journals had higher quality scores than those in specialized journals (p = 0.001), reported adequate allocation concealment more often (p = 0.013), and presented a trial flow diagram more often (p<0.001). We found significant improvements in reporting quality of RCTs published in high-impact factor journals over the last fifteen years. These improvements are likely attributed to concerted international efforts to improve reporting quality such as CONSORT. There is still much room for improvement, especially among specialized journals.


OCT in the monitoring of visual recovery after uneventful retinal detachment surgery.
The aim is to describe 5 cases of unexplained visual impairment after uneventful episcleral surgery associated with submacular lesions occurring post-operatively (bleb-like syndrome). The 5 cases were followed with biomicroscopy and OCT for up to 6 months. At biomicroscopy the 5 eyes presented no visible abnormalities or a yellow subfoveal dot. OCT demonstrated the presence of isolated or multiple subfoveal or submacular blebs. Some cases experienced partial or total slow spontaneous resolution, while other blebs remained stable for months or slightly enlarged. In conclusion, OCT can play an important role in the follow up of patients with unexplained visual impairment after episcleral surgery and diagnose the presence of small subfoveal shallow retinal detachments persistent for months after surgery. We think that OCT should be routinely considered in the follow-up of these patients.


Psychometric Properties of the NIH Toolbox Cognition Battery in Healthy Older Adults: Reliability, Validity, and Agreement with Standard Neuropsychological Tests.
Few independent studies have examined the psychometric properties of the NIH Toolbox Cognition Battery (NIHTB-CB) in older adults, despite growing interest in its use for clinical purposes. In this paper we report the test-retest reliability and construct validity of the NIHTB-CB, as well as its agreement or concordance with traditional neuropsychological tests of the same construct to determine whether tests could be used interchangeably. Sixty-one cognitively healthy adults ages 60-80 completed "gold standard" (GS) neuropsychological tests, NIHTB-CB, and brain MRI. Test-retest reliability, convergent/discriminant validity, and agreement statistics were calculated using Pearson's correlations, concordance correlation coefficients (CCC), and root mean square deviations. Test-retest reliability was acceptable (CCC = .73 Fluid; CCC = .85 Crystallized). The NIHTB-CB Fluid Composite correlated significantly with cerebral volumes (r's = |.35-.41|), and both composites correlated highly with their respective GS composites (r's = .58-.84), although this was more variable for individual tests. Absolute agreement was generally lower (CCC = .55 Fluid; CCC = .70 Crystallized) due to lower precision in fluid scores and systematic overestimation of crystallized composite scores on the NIHTB-CB. These results support the reliability and validity of the NIHTB-CB in healthy older adults and suggest that the fluid composite tests are at least as sensitive as standard neuropsychological tests to medial temporal atrophy and ventricular expansion. However, the NIHTB-CB may generate different estimates of performance and should not be treated as interchangeable with established neuropsychological tests.


[Synthesis of terminal disaccharide of Forssman antigen and its analogs as spacer glycosides and free disaccharides].
Spacered terminal disaccharide of Forssman's antigen GalNAc alpha 1-3GalNAc beta 1-Osp, its analog GalNAc alpha 1-3GalNAc alpha 1-Osp, and disaccharides Gal beta 1-3GalNAc beta 1-Osp and Gal alpha 1-3GalNAc alpha 1-Osp [where sp denotes the (CH2)3NHCOCF3 spacer] were synthesized. Spacered disaccharides were obtained from the (3-trifluoroacetamidopropyl)-2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D- galactopyranoside and its alpha- and beta-analogs in which the 2-azido group was substituted for the 2-acetamido group. The azide glycosyl acceptors gave higher yields of the disaccharides. Azide glycosyl acceptors were prepared by the stereoselective glycosylation of 3-trifluoroacetamidopropanol with a mixture of 1-O-acetates of the 2-azido-3,4,6-tri-O-acetyl-2-deoxy-D-galactopyranose anomers in the presence of Lewis acids. Disaccharides Gal alpha 1-3GalNAc and GalNAc alpha 1-3GalNAc were obtained from the benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-alpha-D-galactopyranoside.


[Hemodynamics in the right gastroepiploic artery and its practical application].
To study functional anatomy of the right gastroepiploic artery (RGEA), its gastric and omental branches and practical significance of these anatomical features. We analyzed 20 cadaveric organ complexes (11 men and 9 women, aged 49-85 years) between 2018 and 2019. The organ complexes consisted of the stomach, proximal duodenum and large omentum. RGEA catheterization at the level of pylorus was followed by selective real time angiography. We assessed the following parameters of RGEA: total length, diameter at the level of pylorus, number and diameter of gastric and omental branches. To objectify the study, we visually divided RGEA into 5 equal segments between pylorus and the last branch arising from this artery. The RGEA looks like a gradually and evenly narrowing tube. Mean diameter of the artery at the level of pylorus was 2.2±0.68 mm, mean length - 23.6±3.7 cm. Mean number of gastric and omental branches was 16.2±4.8 and 8.6±2.6, respectively. The number of gastric branches in the distal part of the RGEA increased, while the diameters of the gastric branches did not significantly differ. The number of gastric branches in distal RGEA increased, while diameters of gastric branches were similar. The greatest number of omental branches with the largest diameter was observed in the 2nd and 3rd segments of the artery. Considering these data, we formulated the equation for RGEA hemodynamics and developed the technique for optimal blood supply to proximal part of the gastric transplant during esophagogastroplasty. Anatomical features of the right gastroepiploic artery can be used in reconstructive surgery of abdominal cavity and chest.


Silencing of MGMT expression by promoter hypermethylation in the metaplasia-dysplasia-carcinoma sequence of Barrett's esophagus.
To determine the relevance of MGMT in Barrett's carcinogenesis, we analyzed promotor hypermethylation and expression of MGMT in Barrett's adenocarcinomas and its paired precursor lesions from 133 patients using a methylation-specific PCR, real-time RT-PCR and immunohistochemistry. Hypermethylation was detected in 78.9% of esophageal adenocarcinomas, in 100% of Barrett's intraepithelial neoplasia, in 88.9% of Barrett's metaplasia, but only in 21.4% of normal esophageal mucosa samples (P<0.001) and correlated significantly with downregulation of MGMT transcripts (P=0.048) and protein expression (P=0.02). Decrease of protein expression was significantly correlated with progressed stage of disease, lymph node invasion and tumor size. We conclude, that aberrant promoter methylation of MGMT is a frequent and early event during tumorigenesis of Barrett's esophagus. High prevalence of MGMT hypermethylation may represent a candidate marker for improved diagnosis and targeted therapy in Barrett's adenocarcinoma.


RNA polymerase activity and uterine growth: Differential stimulation by estradiol, estriol, and nafoxidine.
We have shown previously that estradiol, estriol, and Nafoxidine (Upjohn 11, 100A) have differential effects on uterine growth and that these effects are associated with the retention of the estrogen receptor by the nucleus. In order to examine these relationships further, we have studied the effect of these hormones on endogenous nuclear RNA polymerase I and II in the immature rat uterus. All three compounds caused a rapid elevation in polymerase II activity that reached a peak by the first hour and declined to almost control levels by 2 h after the injection. This transient peak in polymerase II activity was followed by a second elevation by the fourth hour in estradiol- and Nafoxidine-treated animals which was not observed in estriol-treated rats. The activity of polymerase I increased monotonically to very high levels by 4 h and was maintained 12 h or longer in estradiol- and Nafoxidine-treated animals. A similar elevation was observed in estriol-treated rats but the activity declined very rapidly to control levels by 12 h. The second elevation in polymerase II activity and the sustained stimulation of polymerase I activity were correlated with the stimulation of true uterine growth. These data confirm our previous suggestion that long-term nuclear retention of the receptor is a requirement for true uterine growth and suggest that an obligatory response in the production of true growth is the stimulation of a second rise in polymerase II activity and an elevated and sustained activity of polymerase I.


The Effects of Polyphenol Supplementation in Addition to Calorie Restricted Diets and/or Physical Activity on Body Composition Parameters: A Systematic Review of Randomized Trials.
Background: Both, calorie restricted diets (CRD) and physical activity (PA) are conventional obesity therapies but their effectiveness is usually limited in the long-term. Polyphenols are bioactive compounds that have shown to possess some anti-obesity properties. The synergic effects between dietary polyphenols and CRD or PA on body weight and fat are supported by several animal studies, but evidence in human is still inconsistent. Thus, our aim was to review the combined effects of polyphenol supplementation with CRD and/or PA on body weight and fat, body mass index (BMI) and waist circumference (WC) in overweight or obese adults. Methods: Electronic databases (PubMed, Web of Science and Cochrane CENTRAL) were searched for randomized clinical trials (RCT) examining the combination of polyphenols with CRD and/or PA (up to December 31st, 2019). Articles were included if they had a duration of intervention ≥ 4 weeks. Both, quality and risk of bias of the included studies were assessed using the Cochrane RoB2 Tool. Results: The review included 4 and 11 RCTs investigating the anti-obesity effects of polyphenol supplementation combined with CRD and PA, respectively. Isoflavone supplementation may increase fat loss during exercise among post-menopausal women in non-Asian studies. In the rest of RCTs regarding polyphenol supplementation and CRD or PA, no additive changes were found. Conclusion: The results do not yet support polyphenol supplementation as a complementary strategy for enhancing the effectiveness of CRD and PA on weight and fat loss. However, this review suggests that isoflavone and soy products combined with lifestyle changes, especially exercise, provide additional anti-obesity effects in postmenopausal women. The potential role of polyphenols alone or, especially, in addition to conventional therapies (CRD and PA) mostly remains uncertain; and therefore, larger and longer RCTs examining these effects are needed. Protocol Registration: PROSPERO CRD42020159890.


Inotersen and severe thrombocytopenia: 2 case reports and review.
Hereditary transthyretin amyloidosis (hATTR) is an ultra-rare illness. Inotersen is a 2'-O-methoxyethyl (2'MOE)-modified antisense oligonucleotides (ASO) approved in 2018 as a polyneuropathy treatment for adults with hereditary transthyretin amyloidosis stages 1 or 2. Inotersen can produce grade 4 thrombocytopenia as a severe adverse reaction that can lead to potentially fatal hemorrhage complications. We describe our experience in the management of severe thrombocytopenia with inotersen. The onset of the thrombocytopenia and the incidences described in the cases in our hospital are different from that described in the literature. Also, recovery of platelet levels was faster in our patient who was administered human immunoglobulin G, which suggests that there is an immunological component.


Aging and microcirculatory dynamics in human gingiva.
There have been no published reports characterizing gingival vascular function in humans of different ages. In this study, we compared gingival vascular dynamics in 60 healthy male humans ranging in age from 18-75 years (young, 18-25 years (Y); middle, 35-45 years (M); old, 65-75 years (O), 20 subjects/group). Both videomicroscopy of individual microvessels and laser doppler flowmetry were employed to assess marginal gingival circulation. Systemic cardiopulmonary parameters were monitored as controls. The number of gingival vessels visible in a microscopic field was higher and the number of microvessels exhibiting active flow was lower in M and O compared to Y. There were no differences among age groups in laser doppler flow values (tissue blood flow) or in red blood cell velocity in individual vessels. Although not statistically significant with age there was a trend towards decreasing blood flow velocity in both the laser doppler and videomicroscopic measurements. Blood pressure increased slightly with age. Peripheral oxygen saturation was lower in O compared to Y and M. No differences were seen in heart rate, respiratory rate or end-tidal carbon dioxide concentration. The changes in blood pressure and oxygen saturation were expected. The differences in numbers of visible vessels and the number of vessels with active blood flow may reflect the way the gingival microcirculation adapts with age to changing nutritional needs or to microbial and/or mechanical challenge.


Recent progress on the total synthesis of natural products in China.
An overview of natural products synthesis in Mainland China during the past 10 years is provided. This review only emphasizes the first total synthesis of molecules of contemporary interest and syntheses that helped to correct structures. In addition, some significant results on the novel synthesis and structure-activity relationship (SAR) studies of several natural products are introduced.


Influenza vaccination in HIV-positive subjects: latest evidence and future perspective.
Annual influenza vaccination is recommended for persons with human immunodeficiency virus (HIV) infection. Recent reports indicate that immunizations may increase IIeplication in infected individuals. Generally, vaccination against influenza is well tolerated in both children and adult individuals with HNIVand does not induce significant changes in viral load and CD4+ cell counts. The observed increase in viral replication is usually transient and a clear, measurable progression of the underlying HIV disease is hard to be determined. Several studies reported immunogenicity data in HIV+ population, by comparing diferfent influenza vaccines, adjuvanted or not, and different administration routes. Data are encouraging because an adequate immune response is shown, although split/subunit vaccines do not elicite an efficient immune response in these subjects. New strategies have been evaluated to increase the immune response in immunocompromised patients.The aim of this review is to evaluate tolerability, safety, immunogenicity and efficacy of vaccines actually approved for human use and to consider latest evidence and future perspective in HIV positive subjects.


Leukemia mortality and farming in the prairie provinces of Canada.
An increased risk of leukemia has been previously noted among farmers. To examine the risk of fatal leukemia according to various farming practices in a large cohort of Canadian farm operators. A cohort study of the mortality experience (1971-1987) of male farmers in Manitoba, Saskatchewan and Alberta has been conducted. The census records of 156,242 male farmers identified on the 1971 Census of Agriculture and the corresponding Census of Population were linked to mortality records through 1987. We observed a statistically significant test for trend (p = 0.03) between leukemia mortality and the number of chickens and/or turkeys owned (relative risk for > or = 130 chickens and/or turkeys = 1.32, 95% CI = 0.99, 1.77). No association was observed between leukemia mortality and either insecticide or herbicide use. Further research is necessary regarding why farmers exposed to chickens may be at an increased risk of leukemia.


Bivalirudin: an anticoagulant for acute coronary syndromes and coronary interventions.
Heparin is a commonly used anticoagulant in patients with coronary artery disease but its use does not always result in low rates of ischaemic and bleeding events, so the search for new anticoagulants continues. Thrombin plays a key role in both thrombosis and haemostasis and direct thrombin inhibitors modelled on the hirudin molecule found in the saliva of the medicinal leech, Hirudo medicinalis, have recently been developed. To date, the only direct thrombin inhibitor shown to reduce both the ischaemic and the bleeding complications associated with percutaneous coronary intervention (PCI) is bivalirudin, which is approved for this indication in the US and New Zealand. This agent is currently being studied in patients undergoing PCI with or without glycoprotein IIb/IIIa inhibitors and stenting. Bivalirudin has been shown to significantly reduce the risk of reinfarction in patients with acute myocardial infarction (MI) treated with streptokinase, but its use for this indication is not approved in the US. It may also prove to be beneficial in patients with acute MI treated with other fibrinolytic regimens or with primary or facilitated PCI. Bivalirudin is suitable for use as an alternative to heparin in the majority of patients undergoing PCI and in patients receiving streptokinase for acute MI.


Visually Entrained Theta Oscillations Increase for Unexpected Events in the Infant Brain.
Infants form basic expectations about their physical and social environment, as indicated by their attention toward events that violate their expectations. Yet little is known about the neuronal processing of unexpected events in the infant brain. Here, we used rhythmic visual brain stimulation in 9-month-olds (N = 38) to elicit oscillations of the theta (4 Hz) and the alpha (6 Hz) rhythms while presenting events with unexpected or expected outcomes. We found that visually entrained theta oscillations sharply increased for unexpected outcomes, in contrast to expected outcomes, in the scalp-recorded electroencephalogram. Visually entrained alpha oscillations did not differ between conditions. The processing of unexpected events at the theta rhythm may reflect learning processes such as the refinement of infants' basic representations. Visual brain-stimulation techniques provide new ways to investigate the functional relevance of neuronal oscillatory dynamics in early brain development.


Freezing and Ice Structure Formed in Protein Gels.
Ice structure was photographically analyzed for frozen soy protein curd and egg albumin gel frozen under various conditions. Dendritic ice structure was observed growing from the cooling plate parallel to the direction of the heat flux. The change in the ice structure size was analyzed at different locations from the cooling plate in the plane perpendicular to the direction of heat flux. In accordance with the theoretical relationship proposed by us before, the mean ice structure size was inversely proportional to the moving speed of the freezing front and the proportionality constant was not very much different from the diffusion coefficient of water, showing the important role of the molcular diffusion mechanism in the process of ice crystal growth. For the freezing accompanied with supercooling, the ice structure became very small, reflecting the very rapid moving speed of the freezing front when supercooling ceased. The theoretical model by us had advantages over the models proposed in the literature for its simple theoretical basis and wider applicability.


Chelsea, Pimlico and Belgravia District Nursing Association 1930-1939: A case study.
The case study explores how the expansion of the health services during the interwar period impacted upon the status of district nursing and examines how being a voluntary service shaped district nursing associations. A range of primary sources were used; the Association Annual Reports, the Medical Officer for Health Annual Reports for the Borough of Chelsea, the Ministry of Health records, the archives of the Queen's Nursing Institute (QNI) and the Borough of Chelsea Council Minutes. The Medical Officer for Health Reports and the Council minutes identify efforts to improve environmental factors that impacted upon health. These primary sources briefly note the contribution of the Association suggesting that it was integral to the health care provision but considered a constant. The impact of changes to the 1932 Sunday Entertainments Act provide an interesting juxtaposition between the acknowledged value of district nursing and the constant struggle to fundraise in order to provide home nursing. Throughout the 1930s the Association experienced staff shortages and challenges regarding recruitment. The complexities of payment for municipal health services following the 1929 Local Government Act contributed to the staffing challenges. The move to a block grant in 1938 provided increased stability with regards to income. The case study identifies a contradiction regarding the esteem and value placed upon district nursing associations providing home nursing and the constant challenge of resources. District nursing services face similar challenges and this is the 130th anniversary of the Queen's Nursing Institute.


Solubilization and some properties of gamma-glutamyltransferase from human brain microvessels.
Detergents Triton X-100, sodium deoxycholate, and octyl-beta-D-glucopyranoside, and proteinase papain proved to be excellent agents solubilizing the gamma-glutamyltransferase (gamma-GT) from human brain cortex microvessels. Ficin also solubilized gamma-GT but to a lesser extent than papain. The relative molecular mass of the detergent-solubilized enzyme form was greater than 200,000 (in the presence of Triton X-100). The relative molecular mass of the proteinase-solubilized form was slightly greater than that of albumine. gamma-GTs of microvessels from five human brain regions and from the choroid plexus were tested for their specificity toward acceptors. The best acceptors were found to be (in decreasing order of activity) L-cystine, glycylglycine, L-glutamine, L-methionine, and L-alanine. The findings suggest that the main features of gamma-GT of the human blood-brain barrier are very similar to those of gamma-GTs from other human tissues.


Frequency of assault and severity of injury of psychiatric nurses in relation to the nurses' decision to restrain.
Ethical standards and current law demand that acute care psychiatric patients be treated with respect, using the least restrictive interventions. Unfortunately, as restraint use has decreased, assault and injury of mental health care workers has increased. Violence against those working in acute care psychiatry is a serious global issue that needs further examination. This study provides current, in depth information about the nature, frequency and severity of assaults and injuries of psychiatric nurses. This study also examined assault and injury in relation to the nurse's decision to restrain. The findings of this study were compared with findings of an earlier study carried out by one of the authors (Moylan) prior to the institution of policies, which are more restrictive in the use of restraint. In a sample of 110 nurses from five institutions, 80% of the nurses were assaulted, 65% had been injured and 26% had been seriously injured. Injuries included fractures, eye injuries and permanent disability. The number and severity of injuries have increased significantly since the 1996 study. Nurses who had been injured decided to restrain later in the progression of aggression than those who had not been injured.


Intracisternal TRH analogue RX 77368 stimulates gastric histamine release in rats.
The influence of intracisternal injection of the stable thyrotropin-releasing hormone (TRH) analogue RX 77368 on histamine levels in gastric secretion, interstitial fluid of the fundic submucosa, and portal hepatic circulation was investigated in rats. Intracisternal injection of RX 77368 (10-300 ng) induced a dose-related increase in histamine and acid output measured in the gastric secretion of pylorus-ligated, conscious rats. Intracisternal RX 77368 (300 ng) induced within 20 min a significant twofold histamine increase in interstitial fluid sampled from dialysis fibers implanted into the fundic submucosa. Histamine levels in the hepatic portal circulation were also dose dependently increased by RX 77368 injected intracisternally (30-100 ng), whereas intravenous infusion of RX 77368 (300 ng/30 min) did not significantly modify portal histamine levels. Bilateral cervical vagotomy or atropine pretreatment prevented intracisternal RX 77368-induced rise in hepatic portal levels of histamine, whereas purified gastrin monoclonal antibody 9303, injected at a dose blocking gastrin-stimulated acid secretion, had no effect. These results indicate that RX 77368 acts in the brain to increase gastric histamine secretion through vagal-dependent, muscarinic, nongastrin-mediated mechanisms and suggest a possible role of medullary TRH in the vagal regulation of gastric histamine secretion.


Soluble Hyperbranched Porous Organic Polymers.
Soluble porous organic polymers (SPOPs) are currently the subject of extensive investigation due to the enhanced processability compared to insoluble counterparts. Here, a new concept for the construction of SPOPs is presented, which combines the unique topological structure of hyperbranched polymers with rigid building blocks. By using this facile, one-step strategy, a class of novel SPOPs which possess surface areas up to 646 m2 g-1 have been synthesized. The extended π-conjugated backbone affords the polymers bright fluorescence under UV irradiation. Interestingly, after dissolution in a suitable solvent that was slowly evaporated, the polymers retain a large extent of porosity. The SPOPs are potential candidates for gas storage and separation, photovoltaic, and biological applications. In particular, due to the presence of an internal porous structure and open conformations, they show high drug loading efficiency (1.91 g of ibuprofen per gram), which is considerably higher than conventional porous organic polymers.


Comparison of homeless veterans with other homeless men in a large clinical outreach program.
This paper compares homeless veterans with homeless nonveterans from different eras in an effort to better understand the connection between military service and urban homelessness. Two research questions are addressed based on interviews with over 4,000 homeless men who enrolled in a national outreach program for persons suffering from serious mental illness: First, is there anything unique in the social and personal characteristics of homeless veterans in the 1990s that would help to explain their relatively high prevalence in the homeless population, especially among those who were 19 or younger when the draft ended in 1973? Second, aside from age, are the homeless veterans of the era of the All-Volunteer Force different from homeless veterans who served during the era of the military draft? The results replicate many findings from research in the 1980s showing that even homeless veterans with psychiatric disorders tend to have more personal resources compared to homeless men who did not serve in the Armed Forces. Although veterans from the era of the All-Volunteer Force are different from veterans from the era of the draft, the introduction of the All-Volunteer Force per se does not appear to have changed the composition of the adult male homeless population.


Induction of Labor in an Intubated Patient With Coronavirus Disease 2019 (COVID-19).
In the global coronavirus disease 2019 (COVID-19) pandemic, to date, delivery of critically ill pregnant patients has predominantly been by cesarean. A 27-year-old pregnant woman was admitted to a 166-bed community hospital at 33 weeks of gestation with acute hypoxemic respiratory failure secondary to COVID-19. She underwent mechanical ventilation for 9 days. While ventilated, she underwent induction of labor, resulting in a successful forceps assisted-vaginal birth. She was extubated on postpartum day 5 and discharged on postpartum day 10. The neonate was intubated for 24 hours but was otherwise healthy and discharged home at 36 2/7 weeks postmenstrual age. Critically ill patients requiring mechanical ventilation, in this case due to COVID-19, may undergo induction of labor and vaginal delivery when carefully selected.


Prevalence of Anemia and Iron Deficiency among Palestinian Pregnant Women and Its Association with Pregnancy Outcome.
Anemia is a public health problem especially among pregnant women. This study aimed to investigate the prevalence of anemia and iron deficiency among pregnant women and its association with pregnancy outcome in Hebron Governorate in southern Palestine. This is a cross-sectional study that included 300 pregnant women in their first trimester and 163 babies. Maternal anthropometric and socioeconomic and newborns' data were collected. Complete blood count for study subjects and maternal serum ferritin were measured. The prevalence of iron deficiency anemia among pregnant women was 25.7% and 52% of them had depleted iron stores. When pregnant women were grouped into three hemoglobin (Hb) tertile groups, a significant difference was observed between maternal Hb and newborns' birth weight (P= 0.009), height (P= 0.022), head circumference (P= 0.017), and gestational age (P= 0.012). There was a significant association between maternal serum ferritin and frequency of low birth weight (P= 0.001) and frequency of preterm delivery (P= 0.003). No significant association was observed between maternal anthropometric measures or the socioeconomic status and pregnancy outcomes. Iron deficiency is a moderate public health problem among the study subjects. Maternal Hb and serum ferritin significantly affect pregnancy outcomes.


Septic shock in the elderly.
Antibiotic therapy should be directed toward any recognized or suspected pathogens. Multiple broad-spectrum antibiotics are most often successful. Ancillary measures ensure adequate oxygenation, maintenance of adequate urinary output, and support of the cardiovascular system. A team approach using an intensive care facility should result in an optimum outcome in the management of elderly septic patients.


Metabolism of Oxo-Bile Acids and Characterization of Recombinant 12α-Hydroxysteroid Dehydrogenases from Bile Acid 7α-Dehydroxylating Human Gut Bacteria.
Bile acids are important cholesterol-derived nutrient signaling hormones, synthesized in the liver, that act as detergents to solubilize dietary lipids. Bile acid 7α-dehydroxylating gut bacteria generate the toxic bile acids deoxycholic acid and lithocholic acid from host bile acids. The ability of these bacteria to remove the 7-hydroxyl group is partially dependent on 7α-hydroxysteroid dehydrogenase (HSDH) activity, which reduces 7-oxo-bile acids generated by other gut bacteria. 3α-HSDH has an important enzymatic activity in the bile acid 7α-dehydroxylation pathway. 12α-HSDH activity has been reported for the low-activity bile acid 7α-dehydroxylating bacterium Clostridium leptum; however, this activity has not been reported for high-activity bile acid 7α-dehydroxylating bacteria, such as Clostridium scindens, Clostridium hylemonae, and Clostridium hiranonis Here, we demonstrate that these strains express bile acid 12α-HSDH. The recombinant enzymes were characterized from each species and shown to preferentially reduce 12-oxolithocholic acid to deoxycholic acid, with low activity against 12-oxochenodeoxycholic acid and reduced activity when bile acids were conjugated to taurine or glycine. Phylogenetic analysis suggests that 12α-HSDH is widespread among Firmicutes, Actinobacteria in the Coriobacteriaceae family, and human gut ArchaeaIMPORTANCE 12α-HSDH activity has been established in the medically important bile acid 7α-dehydroxylating bacteria C. scindens, C. hiranonis, and C. hylemonae Experiments with recombinant 12α-HSDHs from these strains are consistent with culture-based experiments that show a robust preference for 12-oxolithocholic acid over 12-oxochenodeoxycholic acid. Phylogenetic analysis identified novel members of the gut microbiome encoding 12α-HSDH. Future reengineering of 12α-HSDH enzymes to preferentially oxidize cholic acid may provide a means to industrially produce the therapeutic bile acid ursodeoxycholic acid. In addition, a cholic acid-specific 12α-HSDH expressed in the gut may be useful for the reduction in deoxycholic acid concentration, a bile acid implicated in cancers of the gastrointestinal (GI) tract.


Anatomical study of lateral circumflex femoral arterial system for the anterolateral thigh flap.
The aim of this study was to increase anatomical knowledge of anterolateral thigh (ALT) flap, vascular system nourishing the flap. Forty thighs of 20 male cadavers of Iranian origin were examined. A total of 189 perforators were identified, mainly as musculocutaneous perforators (89.9%), usually in the middle third of the thigh and arising from the descending branch of the lateral circumflex femoral artery (DLCFA). The mean length of superior and inferior pedicles was 9.2 cm and 4.23 cm, respectively. The caliber of the descending artery and one of its accompanying veins was averagely 2.8 and 3.0 mm, respectively. In 85% of the ALT flaps, the DLCFA connected with the lateral superior genicular artery (SGA). These findings suggest that the number of septocutaneous is less than that of the musculocutaneous perforators in the ALT region. This new consideration of ALT flap perforators makes it possible to elevate a vital flap in a greater number of cases, but it requires a longer and more difficult surgical technique to dissect perforators through the muscles. The distally based ALT flap is a good option for coverage of soft-tissue defects around the knee. Additionally, a potentially supercharged ALT flap may be applied in respect to the superior and inferior pedicles.


Using Functional Independence Measure Subscales to Predict Falls-Rapid Assessment.
Falls remain a major issue in inpatient rehabilitation. Decreased scores on the Functional Independence Measure (FIM), given to every patient, have been shown to predict falls risk. The aim of the study was to extend previous research using FIM to predict falls by using only subscales assessed earliest during admissions to indicate high risk of falls. Retrospective cohort study. Two consecutive samples of patients (n1 = 1,553, n2 = 12,301) admitted to a rehabilitation hospital over 9-month and 5-year periods, respectively, were used to evaluate the predictive utility of using only a small number of FIM subscales. Subscales were selected from those assessed earliest and were related to previously published research on falls risk factors. The metric was developed using a historical data set and was validated with a second, separate group of patients. Receiver operating characteristic curves were used to evaluate predictive utility. The combination of Toileting and Expression subscales yielded a comparable area under the curve to the full FIM, and both were greater than the existing method of falls risk assessment. Likelihood of falling was strongly linearly related to score on the Toileting/Expression metric. The sum of two FIM subscales can be used to predict which patients may fall during their stay in a rehabilitation hospital. The FIM scores are assessed early during a patient's stay, are required for all Medicare patients, and may be useful for simple, rapid, and accurate assignment of falls risk.


Cardiac effects of amiloride in the dog.
The cardiac effects of amiloride, a potassium-sparing diuretic, were investigated in isolated, blood-perfused atrioventricular (AV) node, sinoatrial (SA) node, and papillary muscle preparations of dogs. In AV node preparations, when infused into the posterior septal artery (which supplies mainly the AV node), amiloride in a blood concentration of 0.2 mumole/ml gradually prolonged the functional refractory period at atrial pacing rates of 100, 150, and 200 stimuli/min. The lower the pacing rate, the greater was the prolongation. AV conduction time was increased only with pacing at 200 stimuli/min. In the same preparation, when infused into the anterior septal artery (which supplies the His-Purkinje-ventricular system), amiloride did not appreciably prolong AV conduction time, indicating that intraventricular conduction was unaffected. The configuration of ventricular bipolar electrograms was also unchanged. In SA node preparations, amiloride had a negative chronotropic action which was not antagonized by atropine. In papillary muscle preparations, amiloride had a positive inotropic action and prolonged the effective refractory period but did not change ventricular automaticity. The positive inotropic action of amiloride was not antagonized by carteolol, a beta-adrenoceptor-blocking agent. These results indicate that amiloride may have antiarrhythmic properties.


Applying the rules of just war theory to engineers in the arms industry.
Given the close relationship between the modern arms industry and the military, engineers and other professionals who work in the arms industry should be held accountable to the principles of just war theory. While they do not deploy weapons on the battlefield and are not in the military chain of command, technical professionals nonetheless have a moral duty to abide by principles of jus ad bellum and jus in bello. They are morally responsible both for choosing the companies that employ them (and to whom these companies sell arms) and a well as what types of arms they develop.


[Estimation of ovarian response using multiple predictors of ovarian reserve in women undergoing in vitro fertilization-embryo transfer].
To analyze the value of ovarian reserve markers for predicting ovarian response in women undergoing in vitro fertilization-embryo transfer. According to the ovarian response, 331 patients undergoing oocyte retrieval cycles were divided into of normal, poor, and high response groups. Serum anti-Mvllerian hormone (AMH) was determined using AMH ELISA kit on day 3 of the menstrual cycle, antral follicle count (AFC) was measured using vaginal ultrasound, and basal serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E(2)) levels were detected using chemiluminescence method. Serum AMH and FSH levels, FSH/LH ratio, AFC, and the patients age, but not the basal E(2) level (P>0.05), were correlated with the number of oocytes collected (×1000/ampules of Gn) (P<0.001). AFC and serum AMH were the strongest single predictors for low ovarian response, with the areas under curve (AUC) of 0.855 (0.787-0.924) and 0.832 (0.764-0.900) (P<0.05), and cutoff values of ≤9 and ≤1.88 ng/ml, respectively. AFC was the strongest single predictor for high ovarian response, with an AUC of 0.787 (0.728-0.847) and the cutoff value of ≥15. Logistic regression model found that the combination of AFC, serum AMH and FSH improved the predictive power for poor ovarian response, but not for high ovarian response. AFC, serum AMH, FSH, FSH/LH, and age are all predictors of ovarian response, among which AFC is the strongest single predictor. A multivariable model can improve the predictive power for low ovarian response but not for high ovarian response.


Quantitative methods of analysis of footprinting diagrams for the complexes formed by a ligand with a DNA fragment of known sequence.
The regulation of gene expression is based on the interaction of DNA with different ligands. A model of adsorption was considered that can be applied to the quantitative analysis of footprinting diagrams for the complexes formed by a ligand with a DNA fragment of known structure. This model allows the probabilities of ligand binding to DNA sites with a known sequence to be calculated and the variance of probabilities of ligand binding with a specified binding site to be estimated. The model was used for quantitative analysis of diagrams of DNAse footprinting for the complexes of the dimeric analogue of the antitumor antibiotic netropsin. Experimental and theoretically calculated profiles of distribution of netropsin bound on DNA are in good agreement with one another.


Correlation of Gastrointestinal Symptoms at Initial Presentation with Clinical Outcomes in Hospitalized COVID-19 Patients: Results from a Large Health System in the Southern USA.
We aimed to understand the association of gastrointestinal (GI) symptoms at initial presentation with clinical outcomes during COVID-19 hospitalization. This retrospective, multicenter cohort study included consecutive hospitalized COVID-19 patients from a single, large health system. The presence of GI symptoms was assessed at initial presentation and included one or more of the following: nausea, vomiting, diarrhea and abdominal pain. Patients were divided into three cohorts: Only GI symptoms, GI and non-GI symptoms and only non-GI symptoms. The primary outcome was association of GI symptoms with mortality. Secondary outcomes included prevalence of GI symptoms and survival analysis. A total of 1672 COVID-19 patients were hospitalized (mean age: 63 ± 15.8 years, females: 50.4%) in our system during the study period. 40.7% patients had at least one GI symptom (diarrhea in 28.3%, nausea/vomiting in 23%, and abdominal pain in 8.8% patients), and 2.6% patients had only GI symptoms at initial presentation. Patients presenting with GI symptoms (with or without non-GI symptoms) had a lower mortality rate compared to patients presenting with only non-GI symptoms (20% vs. 26%; p < 0.05). The time from hospitalization to being discharged was less for patients presenting with only GI symptoms (7.4 days vs. > 9 days, p < 0.0014). After adjusting for other factors, the presence of GI symptoms was not associated with mortality (p > 0.05). Among a hospitalized COVID-19 positive Southern US population, 41% patients presented with either diarrhea, nausea, vomiting or abdominal pain initially. The presence of GI symptoms has no association with in-hospital all-cause mortality.


Situs inversus with dextrocardia with multiple cardiac lesions in adult.
Situs inversus with dextrocardia is the malposition most likely to occur with structurally normal heart; generally discovered on routine chest x-ray or physical examination performed for other reasons. These persons experience normal longevity of life and have similar risk of getting acquired disease as that of other person of same age and sex group. Symptoms related to acquired disorder may also lead to discovery of such cardiac malposition. Incidence of congenital cardiac anomalies in dextrocardia with situs inversus is very low globally but its figure in Nepal is not known. We report an adult of 43 years age having situs inversus with dextrocardia associated with multiple cardiac lesions i.e. ventricular septal defect, aortic regurgitation, mitral regurgitation and tricuspid regurgitation.


Genome-wide assessment of population structure and genetic diversity of Chinese Lou onion using specific length amplified fragment (SLAF) sequencing.
Lou onion (Allium fistulosum L. var. viviparum) is an abundant source of flavonols which provides additional health benefits to diseases. Genome-wide specific length amplified fragment (SLAF) sequencing method is a rapidly developed deep sequencing technologies used for selection and identification of genetic loci or markers. This study aimed to elucidate the genetic diversity of 122 onion accessions in China using the SLAF-seq method. A set of 122 onion accessions including 107 A.fistulosum L. var. viviparum Makino, 3 A.fistulosum L. var. gigantum Makino, 3 A.mongolicum Regel and 9 A.cepa L. accessions (3 whites, 3 reds and 3 yellows) from different regions in China were enrolled. Genomic DNA was isolated from young leaves and prepared for the SLAF-seq, which generated a total of 1,387.55 M reads and 162,321 high quality SNPs (integrity >0.5 and MAF >0.05). These SNPs were used for the construction of neighbor-joining phylogenetic tree, in which 10 A.fistulosum L. var. viviparum Makino accessions from Yinchuan (Ningxia province) and Datong (Qinghai province) had close genetic relationship. The 3 A.cepa L. clusters (red, white and yellow) had close genetic relationship especially with the 97 A.fistulosum L. var. viviparum Makino accessions. Population structure analysis suggested entire population could be clustered into 3 groups, while principal component analysis (PCA) showed there were 4 genetic groups. We confirmed the SLAF-seq approach was effective in genetic diversity analysis in red onion accessions. The key findings would provide a reference to the Lou onion germplasm in China.


Heparin modulation of the neurotropic effects of acidic and basic fibroblast growth factors and nerve growth factor on PC12 cells.
Nerve growth factor (NGF) and acidic or basic fibroblast growth factor (aFGF and bFGF, respectively) induce neurite outgrowth from the rat pheochromocytoma cell line, PC12. The neurites induced by these three factors are stable for up to a month in cell culture in the continued presence of any of the above growth factors. bFGF (ED50 = 30 pg/ml) is 800 fold more potent in stimulating neurite outgrowth than aFGF (ED50 = 25 ng/ml) and 260 fold more potent than NGF (ED50 = 8 ng/ml). While the neurotropic activities of aFGF and NGF are potentiated by heparin, that of bFGF is both partially inhibited or stimulated, depending upon the concentration of bFGF. Radioreceptor binding experiments show that aFGF and bFGF bind to a common binding site on the PC12 cell surface. Affinity labeling studies demonstrate a single receptor with an apparent molecular weight of 145,000 daltons, which corresponds to the high molecular weight receptor identified in BHK-21 cells. NGF does not appear to compete with aFGF or bFGF for binding to the receptor. Heparin blocked the binding of bFGF to the receptor but had only a small inhibitory effect on the binding of aFGF to the receptor. Thus, it appears that heparin inhibition of the neurotropic effects of bFGF occurs, at least in part, by impairing the interaction of bFGF with the receptor, while having little effect on that of aFGF. The stimulatory effects of heparin on the neurotropic activity of aFGF, bFGF, and NGF may occur through a site not associated with the respective cellular receptor for the growth factors.


Human T-cell Lymphotropic Virus Type I Associated with Amyotrophic Lateral Sclerosis Syndrome: Immunopathological Aspects and Treatment Options.
Human T-cell lymphotropic virus type I (HTLV-I) is a retrovirus related to infectious myelopathies, neoplasms, lymphomas, leukemias, and amyotrophic lateral sclerosis (ALS). It is acquired through sexual transmission, transfusion of blood products, and breastfeeding. The increased expression of human endogenous retrovirus K (HERV-K) in the brain tissue of patients with ALS has been demonstrated, a finding that supports the relationship between the virus and this disease. Therapeutic options include supportive measures and symptomatic treatment with anti-inflammatory medications including steroids, cyclosporines, pentoxifylline, danazol, interferons, and vitamin C. New management proposals are being implemented with valproic acid that acts to facilitate the recognition of the virus by the immune system and with zidovudine antivirals focused on reducing viral load. The purpose of this paper is to describe a clinical case that exhibits clinical signs and evidence of motor neuron compromise as described in electrophysiology studies along with positive laboratory tests for the HTLV-I virus.


[Organization of quality control of the forensic medical investigations].
The article describes the system of quality control at all stages of forensic chemical investigations (including pre-analytical, analytical, and post-analytical ones) carried out by the Saint-Petersburg Bureau of Forensic Medical Expertise It is shown that standardization and control taken together make up a solid foundation for obtaining the reliable and reproducible results of forensic chemical investigations. Responsibility for the quality control at all stages of forensic chemical investigations lies on the heads of the respective departments. Special staff members are appointed to supervise performing each concrete form of control and keeping the relevant documentation.


The role of computerized tomography in shoulder arthrography.
Double contrast computerized tomographic (CT) shoulder arthrograms of 55 shoulders were reviewed. This investigation was compared with conventional arthrograms and the findings were correlated with subsequent clinical and surgical follow-up. CT arthrograms were found to be useful in demonstrating bony, ligamentous and cartilaginous structures and have helped the surgeon in deciding the approach and type of surgical procedure. Indications for CT arthrography are recurrent dislocation, multidirectional instability, severe rheumatoid arthritis and other arthritides, complex shoulder deformities and suspected loose bodies. We found that this examination was not as helpful for rotator cuff injuries, impingement syndrome, adhesive capsulitis and in cases of vague or mild shoulder pain.


A biomimetic gelatin-based platform elicits a pro-differentiation effect on podocytes through mechanotransduction.
Using a gelatin microbial transglutaminase (gelatin-mTG) cell culture platform tuned to exhibit stiffness spanning that of healthy and diseased glomeruli, we demonstrate that kidney podocytes show marked stiffness sensitivity. Podocyte-specific markers that are critical in the formation of the renal filtration barrier are found to be regulated in association with stiffness-mediated cellular behaviors. While podocytes typically de-differentiate in culture and show diminished physiological function in nephropathies characterized by altered tissue stiffness, we show that gelatin-mTG substrates with Young's modulus near that of healthy glomeruli elicit a pro-differentiation and maturation response in podocytes better than substrates either softer or stiffer. The pro-differentiation phenotype is characterized by upregulation of gene and protein expression associated with podocyte function, which is observed for podocytes cultured on gelatin-mTG gels of physiological stiffness independent of extracellular matrix coating type and density. Signaling pathways involved in stiffness-mediated podocyte behaviors are identified, revealing the interdependence of podocyte mechanotransduction and maintenance of their physiological function. This study also highlights the utility of the gelatin-mTG platform as an in vitro system with tunable stiffness over a range relevant for recapitulating mechanical properties of soft tissues, suggesting its potential impact on a wide range of research in cellular biophysics.


POPULATION BIOLOGY OF THE TRANS-ARCTIC EXCHANGE: MtDNA SEQUENCE SIMILARITY BETWEEN PACIFIC AND ATLANTIC SEA URCHINS.
MtDNAs from 2 protein coding regions comprising 576 base pairs were sequenced from 17 individual sea urchins of the species Strongylocentrotus pallidus collected from the north Pacific and north Atlantic oceans. Twelve of 17 individual sequences were identical. Two of these were further sequenced in a third, 441 base pair region, and were also found to be identical. We show how to interpret these results using a simplified Markov model of mtDNA evolution at silent sites. The model was calibrated using 3 urchin species with a published fossil record, and shows that identical S. pallidus mtDNAs in different oceans shared a common ancestor at most 90,000-150,000 years ago (95% confidence interval of upper limit of divergence). The Markov model, used to examine patterns of genetic distance within and between species, shows unexpected variation in the rate of base substitution. The rate of change of G's at fourfold sites is nearly 20 times greater than the rate of change of C's. At twofold sites, this range is less extreme, although purines consistently have a higher rate of change than pyrimidines. Striking genetic similarity and recent genetic exchange between oceans for these urchins is in marked contrast to most other trans-Arctic marine populations, which usually show morphological and genetic differentiation at the species or subspecies level. Recent fossil evidence shows that the north Atlantic and northeastern Pacific have been the scene of radical faunal changes during the Pliocene and Pleistocene. The genetic results presented here extend this conclusion to intraspecific patterns of genetic variability, and direct attention to the northwest Pacific where higher productivity and less environmental change may have left a heritage of greater marine genetic diversity.


Microsurgical instrument handling systems. A new approach to instrument budget control.
1. Large portion of a hospital's supply budget is allocated for repair and replacement of surgical instruments. Microsurgical instrumentation can account for 18% or more of a total OR budget. 2. Managing the surgical instrument repair and replacement budgets with greater emphasis on accountability can help demonstrate effective cost containment. Cost savings may be experienced through appropriate use of surgical instrument management systems for handling, sterilization, and storage of microsurgical instruments. 3. Many facilities are implementing quality control programs to minimize replacement and repair costs, to ensure surgical instrument integrity, and to extend the life of their investment. Education, management information systems, improved communication, and appropriate use of instrument handling systems are some components of budget accountability in the operating room.


Genotypic, phenotypic, and proteomic characterization of Candida glabrata during sequential fluconazole exposure.
Candida glabrata is a major pathogen in humans known to be intrinsically resistant to fluconazole. However, genotypic, phenotypic, and proteomic changes associated with reduced susceptibility to fluconazole are not properly understood. The aim of this study was to observe specific phenotypic, chromosomal, and proteomic alterations in a Candida glabrata strain sequentially exposed to fluconazole. Candida glabrata was exposed to increased concentrations of fluconazole in RPMI for 55 days. Phenotypic changes were evaluated using standard assays. Molecular/proteomic changes in C. glabrata were analyzed by contour-clamped homogeneous electric field electrophoresis, reverse transcription-polymerase chain reaction, and mass spectrometry. Candida glabrata demonstrated increased fluconazole resistance (>256 μg/mL), with extensive cross-resistance to ketoconazole (0.38-3.0 μg), itraconazole (8 to >32 μg), and voriconazole (0.125-1.5 μg). Morphologically dissimilar colonies on RPMI/fluconazole agar demonstrated variable chromosomal profiles compared with the control isolate. Stable chromosomal changes were associated with a significantly higher (P<0.05) mRNA level of the hemolysin gene compared with the control. Phenotypic switching on CuSO4 agar was associated with variable metallothionein mRNA transcription levels. The proteome analysis of a fluconazole-resistant offshoot demonstrated a total of 98 protein spots, 25 showing a twofold upregulation. Fluconazole exposure initiates the chance evolution of a new colonizing population with specific virulence traits.


Genomic imprinting and epigenetic control of development.
Epigenetic mechanisms are extensively utilized during mammalian development. Specific patterns of gene expression are established during cell fate decisions, maintained as differentiation progresses, and often augmented as more specialized cell types are required. Much of what is known about these mechanisms comes from the study of two distinct epigenetic phenomena: genomic imprinting and X-chromosome inactivation. In the case of genomic imprinting, alleles are expressed in a parent-of-origin-dependent manner, whereas X-chromosome inactivation in females requires that only one X chromosome is active in each somatic nucleus. As model systems for epigenetic regulation, genomic imprinting and X-chromosome inactivation have identified and elucidated the numerous regulatory mechanisms that function throughout the genome during development.


Measurement of particle optical absorption, imaginary refractive index, mass concentration, and size at First International LAAP Workshop.
The modified integrating plate method was used in conjunction with ancillary equipment to obtain the absorption coefficient, specific absorption, and single-scattering albedo for a variety of generated aerosols. A computer driven multichannel optical particle counter also provided real-time output for particle size distributions. Size segregated sampling was done for appropriate aerosols, and inferences made on values for the complex refractive index. A new technique (paper in preparation) was also used for samples having low values of absorption, and results for these samples are included. These results are considered the most accurate and take precedence over values obtained by the original method (retained for completeness and inter-comparison purposes).


Activation of cardiac sympathetic afferents: effects of exogenous adenosine and adenosine analogues.
Adenosine is released during myocardial ischemia and can cause angina-like chest pain when given by intracoronary administration. We tested the hypothesis that intracoronary adenosine activates cardiac sympathetic afferent fibers and results in reflex sympathoexcitation. In dogs with sinoaortic denervation and vagotomy, we administered 2 mg of adenosine into the left anterior descending artery over 2 min. Before dipyridamole infusion, intracoronary adenosine resulted in no change in blood pressure or renal sympathetic nerve activity. After dipyridamole infusion, which blocks adenosine uptake, intracoronary adenosine resulted in a peak increase in sympathetic activity of 34 +/- 7%. We also investigated the adenosine-receptor subtype responsible for this sympathoexcitatory response. We found that the adenosine1 agonist N6-cyclopentyladenosine elicited a dose-dependent sympathoexcitatory response similar to adenosine but that the adenosine2 agonist 5'-(N-cyclopropyl)carboxamidoadenosine failed to elicit a sympathoexcitatory response. We conclude that adenosine activates cardiac sympathetic afferent fibers and leads to a sympathoexcitatory response due to activation of adenosine1 receptors.


In situ Ia expression on brain cells in the rat: autoimmune encephalomyelitis-resistant strain (BN) and susceptible strain (Lewis) compared.
In order to examine in situ Ia expression on brain cells of various strains of rat, experimental autoimmune encephalomyelitis (EAE) was induced in both EAE-susceptible (LEW) and EAE-resistant (BN) strains. For induction of EAE in the resistant strain, two methods were applied: one was injection of guinea-pig myelin basic protein (GPBP) in complete Freund's adjuvant into LBNF1----BN chimeras; the other was transfer of GPBP-reactive T-line cells from BN rats into syngeneic rats. LBNF----BN chimeras developed clinical EAE, whereas BN rats that received T-line cells did not. However, histological EAE was apparent in both groups. Immunohistochemical examination using two different monoclonal antibodies (OX3 and OX6) against rat Ia antigens revealed that microglia of LEW, BN and chimera rats expressed Ia antigens in the central nervous system (CNS) with EAE. On the other hand, astrocytes were negative for Ia antigens in all the strains. Furthermore, quantitative analysis was undertaken in order to compare the density of Ia-positive microglia in the BN CNS with that in the LEW CNS. It was revealed that the density of Ia-positive microglia in the vicinity of perivascular inflammatory cell aggregates was essentially the same in both strains regardless of the difference in methods of EAE induction or histological severity of the disease. Ia-positive microglia remote from inflammatory cell aggregates were somewhat fewer in rats with mild histological EAE. However, no strain difference was noted in this analysis. Therefore, we concluded that in situ Ia-inducibility on the brain cells of EAE-resistant rats is not different from that of EAE-susceptible rats. Although Ia-positive microglia in both strains may be involved in the immune responses in the CNS, it is unlikely that the difference in Ia-inducibility on brain cells would contribute to strain-specific susceptibility to EAE.


Simultaneous Assessment of Cardiomyocyte DNA Synthesis and Ploidy: A Method to Assist Quantification of Cardiomyocyte Regeneration and Turnover.
Although it is accepted that the heart has a limited potential to regenerate cardiomyocytes following injury and that low levels of cardiomyocyte turnover occur during normal ageing, quantification of these events remains challenging. This is in part due to the rarity of the process and the fact that multiple cellular sources contribute to myocardial maintenance. Furthermore, DNA duplication within cardiomyocytes often leads to a polyploid cardiomyocyte and only rarely leads to new cardiomyocytes by cellular division. In order to accurately quantify cardiomyocyte turnover discrimination between these processes is essential. The protocol described here employs long term nucleoside labeling in order to label all nuclei which have arisen as a result of DNA replication and cardiomyocyte nuclei identified by utilizing nuclei isolation and subsequent PCM1 immunolabeling. Together this allows the accurate and sensitive identification of the nucleoside labeling of the cardiomyocyte nuclei population. Furthermore, 4',6-diamidino-2-phenylindole labeling and analysis of nuclei ploidy, enables the discrimination of neo-cardiomyocyte nuclei from nuclei which have incorporated nucleoside during polyploidization. Although this method cannot control for cardiomyocyte binucleation, it allows a rapid and robust quantification of neo-cardiomyocyte nuclei while accounting for polyploidization. This method has a number of downstream applications including assessing the potential therapeutics to enhance cardiomyocyte regeneration or investigating the effects of cardiac disease on cardiomyocyte turnover and ploidy. This technique is also compatible with additional downstream immunohistological techniques, allowing quantification of nucleoside incorporation in all cardiac cell types.


Prevalence of thyroid dysfunction in patients with COVID-19: a systematic review.
Currently, there is an increasing interest regarding the impact of COVID-19 on the thyroid function. As several recent reports have described the onset of thyroid dysfunction in patients diagnosed with COVID-19, we performed a systematic review to assess the prevalence of thyroid dysfunction in patients with COVID-19 as this information could be clinically relevant for the management of these patients. A comprehensive computer literature search using PubMed/Medline and Cochrane databases was performed until November 14, 2020 to search original articles evaluating thyroid dysfunction in COVID-19 patients. Information about thyroid dysfunction assessed by thyroid function test was retrieved by the eligible articles. Qualitative analysis (systematic review) only was performed whether a significant heterogeneity of data was detected. Seven studies including 1237 patients with COVID-19 were included. A significant heterogeneity across the studies was found. Most COVID-19 patients were euthyroid with TSH levels in the normal range (from 44 to 94% of the COVID-19 patients assessed in the included studies). The prevalence of thyroid dysfunction in COVID-19 patients (defined as abnormal thyroid function tests) largely varies among the included studies between 13 and 64% of COVID-19 patients as well as clinical presentation. A positive correlation between thyroid dysfunction and clinical severity of COVID-19 was reported. Literature data show that thyroid dysfunction is present in a significant percentage of patients with COVID-19. Assessment of thyroid function may be considered in symptomatic COVID-19 patients to have a baseline before introducing thyroid-interfering drugs and those requiring high-intensity care. Further, well-designed studies are needed to better elucidate the impact of COVID-19 on thyroid function and inform thyroid function testing and thyroid dysfunction management in COVID-19 patients.


Long-term results of microlumbar discectomy.
A long-term prospective study was carried out of 100 consecutive patients undergoing microlumbar discectomy (MLD) and fulfilling stringent selection criteria. A 95% long-term follow-up result was obtained at a mean duration of 8.6 years. At the 7-11-year assessment, 88% of patients had an excellent result, 5% a good result and 7% had either a poor result or new symptoms. Ten patients (10.5%) underwent repeat MLD during the course of the study; nine of the ten reoperations were performed at the same level as the original surgery. The percentage with an excellent result remained relatively constant (88-89%) throughout the study. No reliable predictors of long-term outcome were identified. The results suggest that microlumbar discectomy compares favourably with other surgical techniques with regard to long-term outcome.


Agnosia, alexia and a remarkable form of amnesia in an adolescent boy.
Childhood cases of global anterograde amnesia, visual agnosia or alexia without agraphia, either alone or in any combination, are extremely rare. Here we report the case of a male adolescent, Neil (a pseudonym), who consequent to a pineal tumour began to exhibit all three disorders in the presence of normal verbal intelligence. The most surprising aspect of Neil's case, however, is his ability to retrieve postmorbid memories through the act of writing without being able to provide any oral account of the content of his written reports. His memory retrieval thus has some of the character of 'automatic writing'. This evidence pointing to Neil's possession of a dissociated form of episodic memory presents a new challenge to our understanding of the organization of memory and of the cerebral systems underlying it.


Papillary Carcinoma of Breast: Clinicopathological Characteristics, Management, and Survival.
To study clinicopathological features, treatment strategies, and prognosis of papillary carcinoma of breast. Material and Methods. Data from 58 patients were retrospectively reviewed from January 2010 to December 2016. Four types of papillary carcinoma (on final resected specimen) were included, i.e., invasive papillary carcinoma (IPC), intracystic (encapsulated) papillary carcinoma (EPC), solid papillary carcinoma (SPC), and papillary DCIS (ductal carcinoma in situ). Various features of the four types were observed and compared. Of the 58 patients, 8 were males (13.7%). The mean age at presentation was 61 years; the mean tumor size was 33 mm. The frequency of each histological type was as follows: IPC (n = 22/38%), EPC (n = 22/38%), SPC (n = 12/20.6%), and papillary DCIS (n = 2/3.4%). Only two patients were ER negative (both IPC). HER-2 Neu was positive in 3 patients only, out of which 2 died of progressive disease (one EPC and one IPC). LN metastasis was present in 3 (5%) patients (one in each of 1st three types) and only one died of bone metastasis that was also Her-2Neu positive. All patients underwent upfront surgery except two patients who had synchronous IDC on the contralateral side. Breast conservation surgery (BCS) was performed in 34 (58.6%) and mastectomy in 22 (37.9%) patients. 13 patients did not undergo invasive axillary staging; the rest of 43 (74%) patients did (32 sentinel biopsy and 11 axillary dissection). Chemotherapy was given to 18 patients (31%), mostly to IPC (n = 12). Only 2 patients had bone metastasis (one was IPC and one EPC). Cancer-related death was observed in 3 patients. For all groups combined, 5-year OS was 98% and DFS was 92%. Overall, papillary carcinoma of the breast has an excellent prognosis, even though less intense treatment modalities were used. It is still difficult to define the optimum management and avoid overtreatment, given the limited data in the literature.


Harnessing the reactivity of ortho-formyl-arylketones: base-promoted regiospecific synthesis of functionalized isoquinolines.
An efficient and base-mediated one-pot regiospecific synthesis of structurally diversified isoquinolines and benzo[h] isoquinolines from easily accessible ortho-formyl-arylketones and aryl/(het)arylmethanamines has been described. Challenging 3-alkynyl/alkenyl isoquinolines and bis-isoquinolines were easily attained through this developed chemistry, which can be further used for various organic transformations. Operational simplicity, high atom-economy, broad substrate scope, functional group tolerance and applicability towards large scale synthesis are the advantageous features of this developed methodology.


The Role of Resveratrol in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review.
Advancing age is one of the risk factors for developing many diseases, including cancer, cardiovascular disorders, and neurodegenerative alterations, such as mild cognitive impairment (MCI), and Alzheimer's Disease (AD). Studies have indicated that supplementation with resveratrol (RSV) might improve cerebrovascular function and reduce the risk of developing dementia. Thus, the aim of this systematic review was to assess the effects of RSV on MCI and AD. MEDLINE-PubMed, Cochrane, and EMBASE were used to perform the search, and PRISMA guidelines were followed. Five studies met the eligible criteria; three with AD and two with MCI. In AD patients, the use of RSV reduces Aβ levels, improves brain volume, reduces the Mini-mental status score, and improves AD scores. In patients with MCI, this polyphenol prevents decline in Standard Volumes of Interest and increases the Resting-state Functional Connectivity score. RSV can activate the human silent information regulator 2/sirtuin 1 (Sirt-1) and can inhibit the cyclooxygenase-2 (COX-2), 5-lipoxygenase, and nuclear factor-κB, resulting in the reduction of the proinflammation pathways. It is also associated with the increase in the levels of interleukin (IL)-10 and reduction of interferon-γ and IL-17. Both anti-inflammatory and antioxidant effects can be related to preventing neurodegenerative diseases, doing maintenance, and enabling the recovery of these conditions directly related to inflammation and oxidative stress. We suggest that the use of RSV can bring beneficial effects to patients with MCI or AD.


Late Jurassic teeth of plesiosauroid origin from the Owadów-Brzezinki Lägerstatte, Central Poland.
Owadów-Brzezinki is currently one of the most promising Upper Jurassic sites in Central Poland, with a wide array of both vertebrate and invertebrate fossil fauna present. The discoveries of large-bodied marine reptiles fossils such as ichthyosaurs, turtles, and marine crocodylomorphs attracted attention to the location. A particular Mesozoic marine group, plesiosaurs, remained to be found, and in this report, we note four isolated teeth with distinguishing apicobasal ridging pattern and elongated, conical shape characteristic for plesiosaurians. The outcomes of the Principal Coordinates Analysis (PCoA) of the largest and most complete tooth specimen ZPAL R.11/OB/T4 enabled us to confirm its classification as Plesiosauroidea. This discovery affirms the importance of the site as the area of mixing between Boreal and Tethyan faunas, expanding the broad spectrum of fossil taxa found in this location. Together with previous findings of plesiosaur material in a nearby region, it provides the evidence for the presence of Plesiosauroidea in Owadów-Brzezinki Lägerstatte.


The chemokine stromal cell-derived factor-1 alpha modulates alpha 4 beta 7 integrin-mediated lymphocyte adhesion to mucosal addressin cell adhesion molecule-1 and fibronectin.
The interaction between the integrin alpha(4)beta(7) and its ligand, mucosal addressin cell adhesion molecule-1, on high endothelial venules represents a key adhesion event during lymphocyte homing to secondary lymphoid tissue. Stromal cell-derived factor-1alpha (SDF-1alpha) is a chemokine that attracts T and B lymphocytes and has been hypothesized to be involved in lymphocyte homing. In this work we show that alpha(4)beta(7)-mediated adhesion of CD4(+) T lymphocytes and the RPMI 8866 cell line to mucosal addressin cell adhesion molecule-1 was up-regulated by SDF-1alpha in both static adhesion and cell detachment under shear stress assays. Both naive and memory phenotype CD4(+) T cells were targets of SDF-1alpha-triggered increased adhesion. In addition, SDF-1alpha augmented alpha(4)beta(7)-dependent adhesion of RPMI 8866 cells to connecting segment-1 of fibronectin. While pertussis toxin totally blocked chemotaxis of CD4(+) and RPMI 8866 cells to SDF-1alpha, enhanced alpha(4)beta(7)-dependent adhesion triggered by this chemokine was partially inhibited, indicating the participation of Galpha(i)-dependent as well as Galpha(i)-independent signaling. Accordingly, we show that SDF-1alpha induced a rapid and transient association between its receptor CXCR4 and Galpha(i), whereas association of pertussis toxin-insensitive Galpha(13) with CXCR4 was slower and of a lesser extent. SDF-1alpha also activated the small GTPases RhoA and Rac1, and inhibition of RhoA activation reduced the up-regulation of alpha(4)beta(7)-mediated lymphocyte adhesion in response to SDF-1alpha, suggesting that activation of RhoA could play an important role in the enhanced adhesion. These data indicate that up-regulation by SDF-1alpha of lymphocyte adhesion mediated by alpha(4)beta(7) could contribute to lymphocyte homing to secondary lymphoid tissues.


[Seeking out this other person, demented but above all human].
The nursing care given to "demented" people is now clearly written into law. From the gathering of facts about the patient's life history, to the planning of tasks to the drawing up of the care plan we seem to have available all the information about them we need, with the exception of what remains of their human identity in the eyes of their family and the care workers. Thereby a simple comment made during a routine meeting with the son of a patient can throw up a multitude of ethical questions.


Study on the Classification Performance of a Novel Wide-Neck Classifier.
A novelty-designed wide-neck classifier (WNC) was proposed to enhance the passing ability and classification efficiency of fine particles. Using computational fluid dynamics (CFD), we studied the flow field and velocity distribution in the newly designed WNC. The velocity of the fluid gradually decreased from the wall to the center and from the cylinder to the cone, which facilitates particle classification and thickening. The Reynolds number (Re) and turbulent intensity (I) inside the WNC were discussed. The turbulent intensity increased with increasing feed velocity and overflow outlet diameter and decreased with increasing feed concentration and spigot diameter. The classification of coal slurry was performed to analyze the performance of WNC. The classification efficiency increased with increasing feed velocity but decreased as the feed concentration, spigot diameter, and overflow outlet diameter increased. The predictive models for classification efficiency influenced by the operational and structural parameters were constructed at high correlation coefficients, and the average error of these models was analyzed at 0.28%. Our results can provide valuable insights into the development of mineral classification.


Expression of inhibin-alpha is regulated synergistically by Wilms' tumor gene 1 (Wt1) and steroidogenic factor-1 (Sf1) in sertoli cells.
Wt1 encodes a zinc finger nuclear transcriptional factor, which is specifically expressed in testicular Sertoli cells and knockdown of Wt1 in Sertoli cells causes male mice subfertility. However, the underlying mechanism is still unclear. In this study, we found that expression of inhibin-α is significantly reduced in Wt1-deficient Sertoli cells. Luciferase assays using the inhibin-α promoter indicated that the inhibin-α promoter is transactivated by the Wt1 A, and B isoforms (-KTS), but not the C, and D isoforms (+KTS). Analysis of the Wt1 responsive element of the inhibin-α promoter region using site-directed mutagenesis showed that the nucleotides between -58 and -49 are essential for Wt1-dependent transactivation of the inhibin-α promoter. ChIP assays indicated that Wt1 directly interacts with the inhibin-α promoter. In addition, the inhibin-α promoter is activated synergistically by Wt1 and Sf1. Mutation of the ligand binding domain (LBD) of Sf1 (residues 235-238) completely abolished the synergistic action between Wt1 and Sf1, but did not affect the physical interaction between these two proteins, suggesting that other factor(s) may also be involved in the regulation of inhibin-α in Sertoli cells. Further studies demonstrated that β-catenin enhances the synergistic activation of Wt1 and Sf1 on the inhibin-α promoter. Given the fact that inhibin-α, a subunit of inhibin, is known to be involved in the regulation of spermatogenesis and testicular steroidogenesis, this study reveals a new regulatory mechanism of inhibin-α in Sertoli cells and also sheds light on the physiological functions of Wt1 in gonad development and spermatogenesis.


Could we use a lower dose of rituximab to treat rheumatoid arthritis in clinical practice: pros and cons?
The CERERRA database provides evidence that low-dose rituximab performs as well as the conventional dose in the real world, thus highlighting the possible pharmacoeconomic impact. In clinical trials, it has been shown that rituximab 500 mg twice, performs as well as 1 g twice, 2 weeks apart, in terms of the American College of Rheumatology (ACR)20 and ACR50, but not the ACR70. The choice should always be made after considering that the IMAGE trial has demonstrated similar radiographic progression after the first 6 months, but with less control, with low-dose rituximab in the first 6 months. A possible alternative can be hypothesized.


Synthesis of conformationally constrained peptidomimetics using multicomponent reactions.
A novel modular synthetic approach toward constrained peptidomimetics is reported. The approach involves a highly efficient three-step sequence including two multicomponent reactions, thus allowing unprecedented diversification of both the peptide moieties and the turn-inducing scaffold. The turn-inducing properties of the dihydropyridone scaffold were evaluated by molecular modeling, X-ray crystallography, and NMR studies of a resulting peptidomimetic. Although modeling studies point toward a type IV beta-turn-like structure, the X-ray crystal structure and NMR studies indicate an open turn structure.


Neurolymphomatosis with Spinal Nerve Root Involvement Demonstrated on 18F-FDG PET/CT.
A 56 years old woman with a diagnosis of diffuse large B-cell lymphoma had dyspnea, weakness in the left upper extremity and vocal cord paralysis after chemotherapy. She underwent cervical, thoracal and lumbosacral magnetic resonance imaging (MRI) however findings on MRI could not entirely explain the symptoms of the patient. Therefore, the patient underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography and the scan revealed focal symmetrical 18F-FDG uptake on the cervical, thoracal and lumbal spinal nerve roots. Considering the symptoms of the patient and cerebrospinal fluid cytology findings, hypermetabolic spinal nerve roots were interpreted as lymphoma involvement.


Optimization of a liquid chromatography-tandem mass spectrometry method for quantification of the plant lignans secoisolariciresinol, matairesinol, lariciresinol, and pinoresinol in foods.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of the four major enterolignan precursors [secoisolariciresinol, matairesinol, lariciresinol, and pinoresinol] in foods. The method consists of alkaline methanolic extraction, followed by enzymatic hydrolysis using Helix pomatia (H. pomatia) beta-glucuronidase/sulfatase. H. pomatia was selected from several enzymes based on its ability to hydrolyze isolated lignan glucosides. After ether extraction samples were analyzed and quantified against secoisolariciresinol-d8 and matairesinol-d6. The method was optimized using model products: broccoli, bread, flaxseed, and tea. The yield of methanolic extraction increased up to 81%, when it was combined with alkaline hydrolysis. Detection limits were 4-10 microg/(100 g dry weight) for solid foods and 0.2-0.4 microg/(100 mL) for beverages. Within- and between-run coefficients of variation were 6-21 and 6-33%, respectively. Recovery of lignans added to model products was satisfactory (73-123%), except for matairesinol added to bread (51-55%).


Testicular macromolecular synthesis in men with varicocele.
The synthesis of DNA, RNA, and protein by varicocele testes with spermatogenic dysfunction was studied by examination of the levels of incorporation of [3H]thymidine, [14C]uridine, and [14C]leucine into the testicular tissue at 31 degrees C in vitro. The results suggest that DNA synthesis by the testis with moderate tubular damage is impaired whereas synthesis of RNA and protein is not. The cell regenerative ability of the testis with moderate tubular damage may be poor in spite of the preservation of testicular cell RNA and protein synthesis.


Cholesterol-years score is associated with development of senile degenerative aortic stenosis in heterozygous familial hypercholesterolemia.
We retrospectively evaluated the frequency and identified the factors associated with the development of aortic stenosis (AS) in 96 patients with heterozygous familial hypercholesterolemia (FH). The frequency of AS was 31% (4/13) and that of critical stenosis was 15% (2/13) in older patients over the age of 70 years. All 4 patients with AS were female aged more than 70 years who were diagnosed with FH when aged more than 60 years. There were no significant differences in conventional coronary risk factors; however, the age at cardiac catheterization, age at diagnosis of FH and the cholesterol-years score (CYS) with AS were significantly higher than those without AS (p=0.006, p=0.017, p=0.021, respectively). In multiple regression analysis, CYS was a significant independent predictor for the development of AS (p=0.037) in 13 older patients over the age of 70 years. These results suggest that physicians should be aware that AS needs attention in older patients with heterozygous FH, especially women who have been diagnosed late in life and those who have been inadequately treated.


Why not the first-person plural in social cognition?
Through the mental alignment that sustains social interactions, the minds of individuals are shared. One interpretation of shared intentionality involves the ability of individuals to perceive features of the action scene from the perspective of the group (the "we-mode"). This first-person plural approach in social cognition is distinct from and preferable to the second-person approach proposed in the target article.


Attenuation control of pyrG expression in Bacillus subtilis is mediated by CTP-sensitive reiterative transcription.
In Bacillus subtilis and other Gram-positive bacteria, pyrimidine-mediated regulation of the pyrG gene, which encodes CTP synthetase, occurs through an attenuation mechanism involving an intrinsic transcription terminator in the pyrG leader region. Low intracellular levels of CTP prevent termination at the attenuator by a mechanism that requires the nontemplate strand sequence GGGC at the pyrG transcription initiation site (first G =+1) and the leader transcript sequence GCUCCC located at the 5' end of the terminator RNA hairpin. In this study, we demonstrate that reiterative transcription adds G residues (up to at least 10) to the 5' end of pyrG transcripts when B. subtilis cells are starved for pyrimidines but not when cells are grown with excess cytidine. Regulated repetitive addition of G residues, as well as pyrimidine-mediated pyrG regulation, requires the sequence GGGC or GGGT at the start of pyrG transcription. Mutational insertion of four extra G residues at the 5' end of the pyrG transcript (i.e., 5'-GGGGGGGC) results in constitutive pyrG expression. We propose that the incorporation of extra G residues by reiterative transcription at the wild-type promoter occurs when normal transcription elongation is stalled at position +4 by low levels of the incoming substrate, CTP, during pyrimidine limitation. The poly(G) extensions on the 5' ends of pyrG transcripts act to prevent transcription attenuation by base pairing with the sequence CUCCCUUUC located in the 5' strand of the terminator hairpin. This control mechanism is likely to operate in other Gram-positive bacteria containing similar pyrG leader sequences.